Telephone Cognitive-Behavioral Therapy for Subthreshold Depression and Presenteeism in Workplace: A Randomized Controlled Trial

Subthreshold depression is highly prevalent in the general population and causes great loss to society especially in the form of reduced productivity while at work (presenteeism). We developed a highly-structured manualized eight-session cognitive-behavioral program with a focus on subthreshold depression in the workplace and to be administered via telephone by trained psychotherapists (tCBT).We conducted a parallel-group, non-blinded randomized controlled trial of tCBT in addition to the pre-existing Employee Assistance Program (EAP) versus EAP alone among workers with subthreshold depression at a large manufacturing company in Japan. The primary outcomes were depression severity as measured with Beck Depression Inventory-II (BDI-II) and presenteeism as measured with World Health Organization Health and Work Productivity Questionnaire (HPQ). In the course of the trial the follow-up period was shortened in order to increase acceptability of the study.The planned sample size was 108 per arm but the trial was stopped early due to low accrual. Altogether 118 subjects were randomized to tCBT+EAP (n = 58) and to EAP alone (n = 60). The BDI-II scores fell from the mean of 17.3 at baseline to 11.0 in the intervention group and to 15.7 in the control group after 4 months (p<0.001, Effect size = 0.69, 95%CI: 0.32 to 1.05). However, there was no statistically significant decrease in absolute and relative presenteeism (p = 0.44, ES = 0.15, -0.21 to 0.52, and p = 0.50, ES = 0.02, -0.34 to 0.39, respectively).Remote CBT, including tCBT, may provide easy access to quality-assured effective psychotherapy for people in the work force who present with subthreshold depression. Further studies are needed to evaluate the effectiveness of this approach in longer terms. The study was funded by Sekisui Chemicals Co. Ltd.ClinicalTrials.gov NCT00885014

The effect of Katsura-uri (Japanese pickling melon, Cucumis melo var. conomon) and its derived ingredient methylthioacetic acid on energy metabolism during aerobic exercise

[Purpose] We investigated the effect of Katsura-uri (Japanese pickling melon; Cucumis melo var. conomon) on energy metabolism during exercise in human and animal studies. Methods Eight healthy men (mean age, 21.4 ± 0.7 years) participated in a single-blind, crossover study. Thirty minutes after ingesting the Katsura-uri drink or placebo drink, they exercised on a cycle ergometer at 40% maximal heart rate for 30 min. Respiratory gas analysis was performed during exercise to examine oxygen consumption and substrate utilization. Blood biochemical parameters were evaluated during exercise. In the animal study, the effect of methylthioacetic acid (MTA), a Katsura-uri derived component was examined in mice. Immediately after running at 25 m/min for 30 min, biochemical parameters in the hind limb muscle and blood of mice were measured. [Results] Oxygen consumption during exercise was higher in the Katsura-uri condition (19.8 ± 3.5 mL/kg/min) than the placebo condition (18.6 ± 3.0 mL/kg/min) (P < 0.05). The elevation of blood lactate was lower in the Katsura-uri condition (1.7 ± 0.4 mM) than the placebo condition (2.2 ± 0.6 mM) 15 min after beginning exercise (P < 0.05). There was a higher positive correlation between lactate concentration and carbohydrate oxidation during exercise in the Katsura-uri condition (R2 = 0.86) compared to the placebo condition (R2 = 0.47). The decrease in intermuscular pH and the increase in blood lactate following exercise were prevented by MTA supplementation (250 ppm) with significant differences in the MTA-supplemented group compared to the control group. [Conclusions] These results suggest that the ingestion of Katsura-uri and/or MTA improves glucose metabolism and acidification in skeletal muscles during exercise in human and animal studies

3-(4-Hydroxy-3-methoxyphenyl) propionic acid contributes to improved hepatic lipid metabolism via GPR41

Abstract 3-(4-hydroxy-3-methoxyphenyl) propionic acid (HMPA) is a metabolite produced by the gut microbiota through the conversion of 4-hydroxy-3-methoxycinnamic acid (HMCA), which is a widely distributed hydroxycinnamic acid-derived metabolite found abundantly in plants. Several beneficial effects of HMPA have been suggested, such as antidiabetic properties, anticancer activities, and cognitive function improvement, in animal models and human studies. However, the intricate molecular mechanisms underlying the bioaccessibility and bioavailability profile following HMPA intake and the substantial modulation of metabolic homeostasis by HMPA require further elucidation. In this study, we effectively identified and characterized HMPA-specific GPR41 receptor, with greater affinity than HMCA. The activation of this receptor plays a crucial role in the anti-obesity effects and improvement of hepatic steatosis by stimulating the lipid catabolism pathway. For the improvement of metabolic disorders, our results provide insights into the development of functional foods, including HMPA, and preventive pharmaceuticals targeting GPR41

Taxifolin Suppresses Inflammatory Responses of High-Glucose-Stimulated Mouse Microglia by Attenuating the TXNIP–NLRP3 Axis

Type 2 diabetes mellitus is associated with an increased risk of dementia, potentially through multifactorial pathologies, including neuroinflammation. Therefore, there is a need to identify novel agents that can suppress neuroinflammation and prevent cognitive impairment in diabetes. In the present study, we demonstrated that a high-glucose (HG) environment elevates the intracellular reactive oxygen species (ROS) levels and triggers inflammatory responses in the mouse microglial cell line BV-2. We further found that thioredoxin-interacting protein (TXNIP), a ROS-responsive positive regulator of the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, was also upregulated, followed by NLRP3 inflammasome activation and subsequent interleukin-1beta (IL-1β) production in these cells. Conversely, caspase-1 was not significantly activated, suggesting the involvement of noncanonical pathways in these inflammatory responses. Moreover, our results demonstrated that taxifolin, a natural flavonoid with antioxidant and radical scavenging activities, suppressed IL-1β production by reducing the intracellular ROS levels and inhibiting the activation of the TXNIP–NLRP3 axis. These findings suggest the novel anti-inflammatory effects of taxifolin on microglia in an HG environment, which could help develop novel strategies for suppressing neuroinflammation in diabetes

Mutation Type and Intracranial Aneurysm Formation in Autosomal Dominant Polycystic Kidney Disease

Background Screening for intracranial aneurysms (IAs) in patients with risk factors of IA is recommended. However, genetic risk factors of IA in patients with autosomal dominant polycystic kidney disease (ADPKD) remain unclear, and genotype–phenotype relationships in IAs in patients with ADPKD have not been clarified. Therefore, we aimed to clarify the associations between germline mutations and IA formation in patients with ADPKD. Methods A total of 135 patients with ADPKD who were evaluated for ADPKD mutations were examined for IA formation in this single‐center observational study. Results The incidence of de novo IA formation was 1.3% per patient‐year. Age at IA diagnosis was younger in patients with frameshift (median, 36 years; P=0.003) and splicing mutations (median, 43 years; P=0.046) than in patients with substitutions (median, 63 years). Multivariable analyses showed that IA was associated with female sex (odds ratio [OR], 3.32 [95% CI, 1.10–10.01]; P=0.03), a family history of IA or subarachnoid hemorrhage (OR, 3.05 [95% CI, 1.07–8.71]; P=0.04), estimated glomerular filtration rate (OR, 0.69 [95% CI, 0.54–0.87]; P=0.002), and splicing mutations (OR, 9.30 [95% CI, 1.71–50.44]; P=0.01). Splicing mutations showed a significant association with IA formation even in subcohorts with minimal risk factors for IA, such as age <50 years (OR, 19.52 [95% CI, 3.22–118.51]; P=0.001), nonhypertension (OR, 49.28 [95% CI, 3.60–673.98]; P=0.004), and nonsmoking behavior (OR, 27.79 [95% CI, 3.49–221.21]; P=0.002). Conversely, substitutions showed significant associations with IA formation in subcohorts such as age ≥50 years (OR, 8.66; 95% CI, 1.43–52.51; P=0.02) and chronic kidney disease stages 4 and 5 (OR, 10.70 [95% CI, 1.05–108.75]; P=0.045). Conclusions Genetic analyses in patients with ADPKD could contribute to IA screening and could be useful for evaluating the prognosis, including complications. IA screening should be recommended for patients with ADPKD who have splicing and frameshift mutations and for older patients or patients with advanced ADPKD who have substitutions

Time series changes in pseudo-R2 values regarding maximum glomerular diameter and the Oxford MEST-C score in patients with IgA nephropathy: A long-term follow-up study.

There is no effectual pathological factor to predict the long-term renal prognosis of IgA nephropathy. Glomerular hypertrophy plays a crucial role in kidney disease outcomes in both experimental models and humans. This study aimed to 1) confirm the long-term prognostic significance of a maximal glomerular diameter (Max GD) ≥ 242.3 μm, 2) test a renal prognosis prediction model adding Max GD ≥ 242.3 μm to the Oxford classification (MEST-C), and 3) examine the time series changes in the long-term renal prognosis of patients with IgA nephropathy. The study included 43 patients diagnosed with IgA nephropathy from 1993 to 1998 at Kameda General Hospital. Renal prognosis with the endpoint of a 50% reduction in estimated glomerular filtration rate (eGFR) or the development of end-stage renal disease requiring dialysis was examined using logistic regression analysis, Cox regression analysis, and the Kaplan-Meier method. Pathological evaluation was performed using MEST-C and Max GD, and the validity of the prediction model was evaluated. Patients with Max GD ≥ 242.3 μm had significantly poor renal prognosis with multivariate Cox analysis (P = 0.0293). The results of the Kaplan-Meier analysis showed that kidney survival rates in the high-Max GD group were significantly lower than those in the low-Max GD group (log rank, P = 0.0043), which was confirmed in propensity score-matched models (log rank, P = 0.0426). Adding Max GD ≥ 242.3 μm to MEST-C improved diagnostic power of the renal prognosis prediction model by renal pathology tissue examination (R2: 3.3 to 14.5%, AICc: 71.8 to 68.0, C statistic: 0.657 to 0.772). We confirm that glomerular hypertrophy is useful as a long-term renal prognostic factor

Visceral to subcutaneous fat ratio as an indicator of a ≥30% eGFR decline in chronic kidney disease.

Whether the visceral-to-subcutaneous fat ratio (V/S ratio) is associated with renal prognosis in patients with chronic kidney disease (CKD) remains unclear. Furthermore, little is known about the effect of sex and the absolute amount of visceral fat accumulation such as visceral fat area (VFA) ≥100 cm2 on the V/S ratio in relation to renal prognosis. In this study, 200 patients with CKD were evaluated for renal prognosis. Survival analyses and logistic regression analyses were conducted, generating time-series pseudo-R2 values. The mean and percent change of the pseudo-R2 values from the 6th year to the 10th year (6Y-10Y Mean and 6Y-10Y Change, respectively) were calculated for determining the cut-off points for the medium-term renal prognosis. Multivariate Cox regression analysis revealed that the V/S ratio was significantly associated with renal outcomes and that the VFA category (VFA ≥ 100 cm2) had significant interactions with the V/S ratio regarding renal prognosis. The hazard ratio (HR) of the V/S ratio was higher in the sub-cohort of VFA < 100 cm2 than in the sub-cohort of VFA ≥ 100 cm2 (HR: 6.42 vs. 1.00). Regarding sex differences, a strong association was noted between the V/S ratio and renal prognosis in women but not in men (HR: 2.40 vs. 1.10). On the other hand, 6Y-10Y Mean of the pseudo-R2 values indicated differences in the cut-off points of the V/S ratio between men and women (V/S ratio: 0.75 vs. 0.5). Our findings indicate that it may be clinically meaningful to consider the differences in sex and the amount of VFA ≥100 cm2 for the V/S ratio in relation to renal outcomes in patients with CKD. The 6Y-10Y Mean of the pseudo-R2 values contributed to determining the cut-off points of the V/S ratio according to the sex difference

Maximum Glomerular Diameter and Oxford MEST-C Score in IgA Nephropathy: The Significance of Time-Series Changes in Pseudo-R2 Values in Relation to Renal Outcomes

The progression of immunoglobulin A nephropathy (IgAN) is currently assessed using the Oxford MEST-C score, which uses five indicators (mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and the presence of crescents) but has not yet included any risk factors related to glomerular size. Therefore, we tested whether adding another indicator, maximal glomerular diameter (Max GD), would improve the prognostic ability of this scoring system. The data of 101 adult patients diagnosed with IgAN between March 2002 and September 2004 were reviewed. We used McFadden&rsquo;s pseudo-R2 and the corrected Akaike information criterion to assess model fit and the concordance (C)-statistic to assess discriminatory ability. A 10 &mu;m increase in Max GD was significantly associated with a composite outcome (&ge;50% decline in the estimated glomerular filtration rate or end-stage renal disease). The receiver operating characteristic analysis determined the cut-off for high vs. low Max GD at 245.9 &mu;m, and adding high Max GD to the MEST-C score significantly improved the model&rsquo;s discrimination of renal outcomes at 5 and &ge;10 years. Thus, including the Max GD in the Oxford classification of IgAN might increase its robustness and provide a more comprehensive prognostic system for clinical settings

Demographic and clinical characteristics of the participants.

<p>The figures in parentheses are either percentages or SD.</p><p>BDI-II: Beck Depression Inventory-II.</p><p>HPQ: World Health Organization Health and Work Performance Questionnaire.</p